Autophagy and Apoptosis in Rabies Virus Replication

Rabies virus (RABV), the prototype member of the genus Lyssavirus in the family Rhabdoviridae, is known to induce two evolutionarily conserved and genetically regulated processes called autophagy and apoptosis in target cells; however, the exact mechanisms behind both processes are not clearly understood. Thus, this report analyses and outlined the molecular mechanisms of RABV induced autophagy and apoptosis, and the effects of such cellular events on RABV replication. The report shows the RABV capacity to stimulate and utilize autophagy during replication through different pathways including N/P proteins directed CASP2 downregulation, inhibition of mTOR, and phosphorylation of AMPK and MAPK to initiate the autophagy. Consequently, the viral P protein frequently binds to the host BECN1 protein to facilitate the nucleation of autophagosomes, and the fusion of autophagosomes with lysosomes leading to an incomplete autophagy. Similarly, cell apoptosis can be activated through diverse ways following RABV invasion: as a defense measure to suppress RABV replication, the level of apoptosis correlates positively with the expression level of RABV G-protein. While, the M and P proteins commonly target mitochondria to induce intrinsic apoptosis through both caspase-dependent and independent pathways. In most RABV infections, a crosstalk between autophagy and apoptosis acts to inhibit RABV replication.
(BNU)